#integrins

Network Management

Like a team of security guards patrolling a large museum, macrophages work as a team to sweep the body for invaders or dead cell material. But while radios and earpieces might help security guards coordinate their action, it’s not clear precisely how macrophages work together to take action where needed, and keep the surveillance work going. Macrophages can travel through tissues by changing shape, flexing, and attaching to surroundings with velcro-like proteins called integrins. Researchers who thought the different forms of motion might influence the network activity investigated what happened if mouse macrophages were engineered to lack integrins. In both lab experiments and living mouse tissue (pictured) the resulting macrophages (yellow) were able to move to injured sites as normal, but could not maintain their usual surveillance behaviour. Individual cells’ movement dictated the whole network’s performance, which could have implications for treatments that aim to regulate inflammation.

Written by Anthony Lewis

Image from work by Neil Paterson and Tim Lämmermann

Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, March 2022

Integrins are important cell membrane receptors that allow cells to bind to the extracellular matrix to facilitate cell movement and migration as well as the transmission of mechanical and chemical information to a cell. During cell migration, integrins bind extracellular ligands and link them to actin filaments within the cell for the transmission of cytoskeletal forces. These cytoskeletal forces are produced by “retrograde flow” of F-actin from the leading edge of a migrating cell driven by polymerization or contraction of actin filaments. Specifically, a polarized actin assembly exerts a force against the cell’s membrane, pushing F-actin toward the center of the cell. For integrins to bind the extracellular ligands, however, they must be activated and undergo a conformational change. It is believed that cytoskeletal forces activate these surface receptors by mediating this conformational change. Following this “cytoskeletal force hypothesis,” it would be expected that activated, ligand-bound integrins at the leading edge of the cell are oriented and aligned.

SBGrid member Tim Springer and other researchers have used polarization-sensitive fluorescence microscopy of fluorescently labeled αVβ3 integrins in fibroblasts to evaluate ligand-bound integrin alignment. Their work demonstrates that the integrins are coaligned within the focal adhesions in migrating cells, dependent on binding immobilized ligands and talin-mediated linkage of integrins to F-actin. Using Rosetta modeling, they modeled the broader range of possible orientations of the integrin with and without the fluorescent label. This work suggests that the integrins in focal adhesions are coaligned and can be tilted by cytoskeletal forces, providing a potential mechanism for sensing directional forces and cues.

Beta-Integrin Implicated In Slow Healing Of Aged Muscles

With age, the function and regenerative abilities of skeletal muscles decrease. Therefore, the elderly can find it difficult to recover from injury or surgery. A new study from the laboratory of Chen-Ming Fan from Johns Hopkins University has shown that a protein called β1-integrin is crucial for muscle regeneration. β1-integrin seems to provide a promising target for therapeutic intervention to…

How Stem Cells Exit The Bloodstream

New research from a laboratory at North Carolina State University has changed our understanding of how therapeutic stem cells exit the bloodstream.  Understanding this new process, which has been given the name “angiopellosis” may not only increase our understanding of how intravenous stem cells home to their target tissues, but also how metastatic cancer cells invade new sites. When white blood…

Integrins are made up of two subunits. The alpha and the beta. The alpha has a domain called the beta propeller. The beta subunit has a domain called the A domain. Some integrins then have an I domain that is attached to the alpha subunit at the beta propeller. The I domain is where the ligand binds. If the integrin doesn't have an I domain, the ligand instead binds at the interface of the beta propeller and the A domain, which are in the alpha and beta subunits, respectively. This binding then causes a conformational change. Specifically helix alpha7 moves downward. Helix alpha7 is located, you guessed it, on the beta subunit.